In vivo antibabesial activity and bioinformatic analysis of compounds derived from the Medicines for Malaria Venture box against Babesia microti

Abstract

Here, we have evaluated the inhibitory effects of Medicines for Malaria Venture (MMV) Malaria Box compounds that exhibited potent in vitro anti-bovine Babesia efficacy against the growth of B. microti in mice and conducted follow-up investigations of the structural similarity between the identified potent MMV compounds and the commonly used antibabesial drugs was performed using atom Pair fingerprints (APfp). Screening the Malaria Box against the in vivo growth of the B. microti parasite helped with the discovery of new, effective anti-bovine Babesia drugs, including MMV667488, MMV007285, and MMV019881. Of note, MMV019881 exhibited the highest anti-B. microti efficacy in vivo among the screened MMV compounds. The APfp results revealed that the maximum structural similarity (MSS) was observed between MMV007285, diminazene aceturate, and imidocarb dipropionate (ID). In the same way, clofazimine (CF) and MMV667488 showed the MSS with either each other based on the analysis. The distance matrix and molecular weight correlation findings highlight the possible potential antibabesial efficacy of MMV667488, ID, and CF when administrated as a combination therapy. In conclusion, in the current study new potent antibabesial drug, MMV019881 was identified. CF and MMV667488 showed the MSS with either each other based on the hierarchical clustering analysis (HCA) and such relation is confirmed by the distance matrix and molecular weight correlation findings. Such combination therapy might have a potential as a novel regime for treating animal or human babesiosis.

Keywords: Babesia bovis; Babesia microti; Drug discovery; MMV007285; MMV019881; MMV667488; Malaria box.